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Biomedical subjects

K Ugurbil

Publications and source records attributed to K Ugurbil.

At least 73 records · Page 4Linked to original sources
PubMed1997

Myocardial bioenergetics during acute hibernation.

During moderate reductions of blood flow, the myocardium downregulates contractile function and ATP utilization to result in reduced but stable ATP levels, recovery or stability of (reduced) creatine phosphate (CP), and preservation of myocyte viability. The intent of this study was to determine the influence of the level of ischemic blood flow and the major determinants of myocardial O2 consumption (MVO2) (heart rate and systolic blood pressure) on recovery of CP during prolonged moderate myocardial hypoperfusion. 31P-nuclear magnetic resonance spectroscopy was used to measure CP, ATP, and Pi in the subepicardium (Epi) and subendocardium (Endo) of 13 open-chest dogs. Wall thickening was measured with sonomicrometry. A coronary stenosis reduced mean myocardial blood flow (microspheres) from 1.10 +/- 0.07 to 0.71 +/- 0.06 ml.g-1.min-1 (P < 0.01) and the Endo-to-Epi blood flow ratio from 1.12 +/- 0.07 to 0.59 +/- 0.06 (P < 0.01), and dyskinesis developed. Coronary blood flow and systolic wall thickening did not change significantly during 4 h of hypoperfusion. Epi CP and ATP fell to 80 +/- 4% (P < 0.05) and 93 +/- 3% of control, respectively, at 30 min. Epi CP then recovered to 87 +/- 5% while ATP decreased further to 83 +/- 5% of baseline by the end of the 240-min ischemic period. Endo CP and ATP fell to 53 +/- 4 and 77 +/- 5% of control, respectively, at 30 min; then Endo CP recovered to 85 +/- 6% while ATP decreased further to 68 +/- 6% of baseline at 240 min of hypoperfusion. ADP levels were significantly increased at 30 min but recovered to baseline by 240 min of hypoperfusion. delta Pi/CP increased significantly (Endo > Epi) at the onset of ischemia and then progressively decreased. At 30 min, mild myocardial acidosis was observed in some hearts with variable pH recovery during continuing hypoperfusion. The data demonstrate that variations in blood flow cannot account for the magnitude of the initial fall in CP or for the final extent of recovery. However, the rate at which CP recovered was significantly correlated with the level of blood flow. Variations in the determinants of MVO2 did not account for differences in CP recovery.

Adenosine Diphosphate↗
PubMed1996

Functional and bioenergetic consequences of postinfarction left ventricular remodeling in a new porcine model. MRI and 31 P-MRS study.

BACKGROUND: The underlying mechanisms by which left ventricular remodeling (LVR) leads to congestive heart failure (CHF) are unclear. This study examined the functional and bioenergetic abnormalities associated with postinfarction ventricular remodeling in a new, large animal model. METHODS AND RESULTS: Remodeling was induced by circumflex coronary artery ligation in young pigs. LV mass, volume, ejection fraction (EF), the ratio of scar surface area to LV surface area, and LV wall stresses were calculated from magnetic resonance imaging anatomic data and simultaneously measured LV pressure. Hemodynamics, transmural blood flow, and high-energy phosphates (spatially localized 31P-nuclear magnetic resonance) were measured under basal conditions, during hyperperfusion induced by pharmacological vasodilation with adenosine, and during pyruvate infusion (11 mg/kg per minute IV). Six of 18 animals with coronary ligation developed clinical CHF while the remaining 12 animals had LV dilation (LVR) without CHF. The results were compared with 16 normal animals. EF decreased from 55.9 +/- 5.6% in normals to 34.6 +/- 2.3% in the LVR group (P < .05) and 24.2 +/- 2.8% in the CHF group (P < .05 versus LVR). The infarct scar was larger in CHF hearts than in LVR hearts (P < .05). In normals, LV myocardial creatine phosphate (CP)/ATP ratios were 2.10 +/- 0.10, 2.06 +/- 0.16, and 1.92 +/- 0.12 in subepicardium (EPI), mid myocardium (MID), and subendocardium (ENDO), respectively. In LVR hearts, the corresponding ratios were decreased to 1.99 +/- 0.13, 1.80 +/- 0.14, and 1.57 +/- 0.15 (ENDO P < .05 versus normal). In CHF hearts, CP/ATP ratios were 1.41 +/- 0.14, 1.33 +/- 0.15, and 1.25 +/- 0.15; (P < .05 versus LVR in EPI and MID). The calculated myocardial free ADP levels were significantly increased only in CHF hearts. CONCLUSIONS: Bioenergetic abnormalities in remodeled myocardium are related to the severity of LV dysfunction, which, in turn, is dependent on the severity of the initiating myocardial infarction.

Adenosine Triphosphate↗
PubMed1996

31P magnetic resonance spectroscopy of the Sherpa heart: a phosphocreatine/adenosine triphosphate signature of metabolic defense against hypobaric hypoxia.

Of all humans thus far studied, Sherpas are considered by many high-altitude biomedical scientists as most exquisitely adapted for life under continuous hypobaric hypoxia. However, little is known about how the heart is protected in hypoxia. Hypoxia defense mechanisms in the Sherpa heart were explored by in vivo, noninvasive 31P magnetic resonance spectroscopy. Six Sherpas were examined under two experimental conditions [normoxic (21% FiO2) and hypoxic (11% FiO2) and in two adaptational states--the acclimated state (on arrival at low-altitude study sites) and the deacclimating state (4 weeks of ongoing exposure to low altitude). Four lowland subjects were used for comparison. We found that the concentration ratios of phosphocreatine (PCr)/adenosine triphosphate (ATP) were maintained at steady-state normoxic values (0.96, SEM = 0.22) that were about half those found in normoxic lowlanders (1.76, SEM = 0.03) monitored the same way at the same time. These differences in heart energetic status between Sherpas and lowlanders compared under normoxic conditions remained highly significant (P < 0.02) even after 4 weeks of deacclimation at low altitudes. In Sherpas under acute hypoxia, the heart rate increased by 20 beats per min from resting values of about 70 beats per min, and the percent saturation of hemoglobin decreased to about 75%. However, these perturbations did not alter the PCr/ATP concentration ratios, which remained at about 50% of the values expected in healthy lowlanders. Because the creatine phosphokinase reaction functions close to equilibrium, these steady-state PCr/ATP ratios presumably coincided with about 3-fold higher free adenosine diphosphate (ADP) concentrations. Higher ADP concentrations (i.e., lower [PCr]/[ATP] ratios) were interpreted to correlate with the Km values for ADP-requiring kinases of glycolysis and to reflect elevated carbohydrate contributions to heart energy needs. This metabolic organization is postulated as advantageous in hypobaria because the ATP yield per O2 molecule is 25-60% higher with glucose than with free fatty acids (the usual fuels utilized in the human heart in postfasting conditions).

Acclimatization↗
PubMed1995

Properties of fructose-1,6-bisphosphate aldolase from Escherichia coli: an NMR analysis.

A class II Zn(2+)-dependent fructose-1,6-bisphosphate (FBP)- aldolase was purified from an overproducer strain of Escherichia coli and characterized by standard biochemical techniques and 13C NMR spectroscopy. The principal finding of these studies was identification, by 13C NMR spectroscopy, of an enzyme-bound reaction intermediate, the enediol(ate) form of dihydroxyacetone phosphate (DHAP). Formation of this intermediate requires the presence of Zn2+ and is pH dependent, with increasing amounts of this tautomer appearing at alkaline pH's. This pH dependence closely parallels the pH activity profile of the enzyme, suggesting an involvement of the enediol-DHAP form in the reaction pathway. In addition to these results the following observations were made on this enzyme: (a) E. coli FBP aldolase binds and utilizes only the carbonyl forms of FBP and DHAP; (b) the function of Zn2+ in this metalloaldolase appears to be polarization of the C = O bond of DHAP; (c) activity of this enzyme is unaffected by glycolytic intermediates or nucleotide phosphates such as ATP. Although these studies provide some information about the catalytic mechanism of E. coli FBP aldolase, they do not provide an explanation for the apparent regulation of this enzyme reported in previous in vivo NMR studies. While the possibility that the enzyme is allosterically regulated cannot be excluded at this time, an interesting possibility suggested by this and other studies is that in E. coli glycolytic substrates may be channeled through a multienzyme complex.

Binding Sites↗
PubMed1995

Transmural distribution of 2-deoxyglucose uptake in normal and post-ischemic canine myocardium.

This investigation was performed to determine (i) whether 31P spatially localized 31P NMR spectroscopy could be utilized to determine the transmural distribution of 2-deoxyglucose (2DG) uptake in the in vivo canine heart and (ii) whether transmural 2DG uptake would be affected by a preceding ischemic insult. 2DG was infused and the accumulation of 2-deoxyglucose-6-phosphate (2DGP) was monitored (by means of spatially localized 31P NMR) in control hearts, in pharmacologically hyperperfused hearts, and in hearts subjected to four (5 min) occlusions of the left anterior descending coronary artery. Myocardial blood flow was measured with radioactive microspheres. In control hearts, subendocardial (ENDO) 2DGP contents were significantly higher than those in the subepicardium (EPI) being 3.8 +/- 0.3 and 2.2 +/- 0.2 mumol/g, respectively; the ENDO/EPI ratio of 2DGP was 1.70 +/- 0.21. During hyperperfusion blood flow increased approximately four-fold but 2DGP accumulation was not altered. ATP levels in post-ischemic myocardium were significantly decreased (ENDO more than EPI) and 2DGP accumulation in each layer was increased (p < 0.01 vs control); however, the ENDO/EPI ratio of 2DGP was not altered. 2DG infusion induced a marked elevation of blood insulin and norepinephrine levels. These data demonstrate that in the presence of high blood levels of 2DG and insulin: (i) 2DGP accumulation can be measured in the in vivo canine heart; (ii) in normal hearts 2DG uptake is more pronounced in the inner layers of the left ventricular wall (this transmural 2DG uptake gradient is not due to subendocardial hypoperfusion); and (iii) 2DG uptake is greater in the post-ischemic heart but the ENDO/EPI gradient of 2DG uptake is not altered indicating that the more severe ischemic insult in the subendocardium does not result in a disproportionate increase in 2DG uptake in that region of the myocardium. Although 2DG uptake patterns in this model most probably reflect those of glucose (at comparable glucose and insulin levels), quantitative extrapolations with regard to the rate of glucose uptake are not possible from the present data.

Animals↗
PubMed1995

An in vivo 31P magnetic resonance spectroscopy study of uridine excess in rats fed orotic acid.

Spatially localized 31P NMR spectroscopy was used to assay in vivo the liver of intact rats fed orotic acid (OA) in a diet which produces hepatic steatosis. Twenty-three sets of multiple volume spectra were obtained from twenty-one 265- to 315-g female rats after 0-9 days of feeding either a 1% OA/64% sucrose diet (12 rats) or a 65% sucrose control diet (9 rats). The intensity of the in vivo diphosphodiester resonance ascribed to UDP-hexos(amin)es increased and the phosphomonoester resonance decreased in intensity prior to fatty infiltration. High resolution NMR spectroscopy of extracts of these livers indicated that the UDP-hexos(amin)e peak included four different UDP-sugars including UDP-N-acetylglucosamine (UDP-glcNAc), and that lower phosphocholine (P-Cho) accounted for the lower phosphomonoester resonance in vivo. Increased UDP-glcNAc is thought to reflect impaired lipoprotein glycosylation as a mechanism for hepatic steatosis in orotic acid feeding. P-Cho deficiency has been shown to be due to an increased rate of phosphatidylcholine synthesis. Low P-Cho concentration has been shown to be associated with lipid accumulation in a choline-deficient diet, but was not previously associated with hepatic steatosis in OA feeding. Changes in phosphorus metabolites were observed 2 days prior to development of fatty liver. HPLC assay of uridine nucleotides showed a good correlation between magnetic resonance spectroscopy and HPLC quantitation. In this study there were two biochemical correlates of impaired hepatic lipid secretion detectable by in vivo assay with 31P NMR spectroscopy. This method has application for noninvasive assays in ornithine transcarbamylase-deficient patients.

Animals↗
PubMed1995

Functional magnetic resonance imaging as a management tool for cerebral arteriovenous malformations.

The location of eloquent cortex, such as the motor strip, the visual cortex, or Broca's area, may be difficult to predict even with multiprojectional magnetic resonance imaging (MRI). Distortion and displacement of this cortex may occur with a congenital lesion, such as an arteriovenous malformation, or by an acquired disease, such as a neoplasm. A desire to avoid damaging these eloquent areas by conventional surgery, radiosurgery, or endovascular surgery makes their accurate identification an important part of the pretherapeutic planning process. Blood oxygen level dependent functional MRI is a technique that uses the local increase of oxyhemoglobin concentration in the patient that occurs as a result of the increase in flow rate and blood volume in eloquent cortex undergoing stimulation from, for example, flashing lights, hand movements, or speech. We have used the blood oxygen level dependent technique to localize eloquent cortex relative to arteriovenous malformations and tumors. Using a 4.0-T magnetic resonance (MR) system, there is a sufficiently high degree of spatial resolution of the MR signal intensity changes during stimulation to allow the identification of eloquent cortex. Alternative, non-MR, invasive techniques for functional localization include electrocorticography and stimulation from subdural grids and strips. Noninvasive, non-MR technologies, such as positron emission tomography and magnetoencephalography, can also provide functional localization of eloquent cortex. However, the perfection of functional MRI at the 1.5-T field strength and the large number of such MR systems in operation mean that a highly accurate cerebral cortical localization technique can be available to most neuroscientists without the need to purchase alternative expensive technology.

Adult↗
PubMed1995

Functional MR imaging of perceptual and cognitive functions.

Functional MR imaging using the blood oxygen level dependent technique as an endogenous contrast agent localizes eloquent cortex when stimulated by a variety of motor or sensory tasks. To date, visual, motor, speech, and cerebellar studies have been conducted, revealing significant information regarding cortical localization and control of various functions. The technique is also an important management tool for localizing eloquent cortex contiguous to a tumor or arteriovenous malformation, so that injury can be avoided if ablation of the lesion is contemplated.

Cerebellum↗
PubMed1994

Myocardial bioenergetic abnormalities in a canine model of left ventricular dysfunction.

OBJECTIVES: The purpose of this study was to assess high energy phosphate compound metabolism in remodeled left ventricular myocardium. BACKGROUND: The development of heart failure several years after myocardial infarction is often unexplained. Certain abnormalities of remodeled myocardium suggest that structural changes occurring in viable myocardium after discrete myocardial damage may contribute to the later appearance of heart failure. Whether these abnormalities alter metabolism in the surviving muscle and thereby possibly contribute to ventricular dysfunction is unknown. METHODS: High energy phosphate compound metabolism was assessed using spatially localized phosphorus-31 nuclear magnetic resonance spectroscopy. Eleven dogs with documented left ventricular dysfunction, resulting from infarction produced by transmyocardial direct current shock, were compared with eight normal dogs. Analyses were performed at baseline and during coronary hyperperfusion induced by intravenous adenosine. Myocardial blood flow was measured with radioactive microspheres. RESULTS: The creatine phosphate/adenosine triphosphate (CP/ATP) ratio was significantly reduced in the left ventricular dysfunction group in both the subepicardium ([mean +/- SE] 1.94 +/- 0.08 vs. 2.32 +/- 0.13, p = 0.019) and the subendocardium (1.71 +/- 0.07 vs. 2.05 +/- 0.07, p = 0.004). Intravenous adenosine produced significant coronary hyperemia in both groups but was less marked in dogs with left ventricular dysfunction. The improvement in myocardial perfusion was accompanied by a significant increase in the subendocardial CP/ATP ratio (from 1.71 +/- 0.07 to 1.92 +/- 0.08, p = 0.01) in dogs with left ventricular dysfunction. CONCLUSIONS: An abnormal transmural distribution of high energy phosphate compounds is evident in remodeled myocardium. This abnormality may be related in part to mismatch of oxygen delivery and demand.

Adenosine↗
PubMed1994

Functional imaging of the motor system.

Recent studies of the motor system using functional imaging have served to emphasize the complexity of the control of even relatively simple movements. The results of these studies suggest that the behavioral context of the movement is an important determinant of functional activation within cortical motor areas.

Functional Laterality↗
PubMed1994

High-energy phosphate responses to tachycardia and inotropic stimulation in left ventricular hypertrophy.

Spatially localized nuclear magnetic resonance (NMR) spectroscopy was used to examine the effect of tachycardia and inotropic stimulation on myocardial ATP, creatine phosphate (CrP), and inorganic phosphate (Pi) in animals with left ventricular hypertrophy (LVH). Studies were performed in eight normal dogs and seven dogs with moderate LVH produced by banding the ascending aorta. 31P-NMR spectra were obtained from five layers across the LV wall, while blood flow (BF) was measured with microspheres during control conditions, pacing at 200 and 240 beats/min, and during dobutamine infusion (Dob). Myocardial ATP and CrP levels were normal in the LVH hearts during control conditions. Pacing did not alter the transmural distribution of perfusion or the levels of CrP, ATP, and Pi in normal hearts. In contrast, in four of seven LVH hearts, pacing decreased the subendocardial/subepicardial (ENDO/EPI) BF ratio and caused depletion of CrP and appearance of Pi characteristic of ischemia in the subendocardium. Dob produced greater increases in the heart rate x LV systolic pressure product (RPP) and greater increases of Pi and decreases of CrP in LVH than in normal hearts; however, at comparable elevations of RPP the alterations of Pi and CrP were similar in both groups. Although Dob decreased the ENDO/EPI in LVH hearts, Dob-induced alterations in CrP and Pi were uniform across the LV wall. Increasing myocardial BF with adenosine or carbochromen did not reverse the alterations in Pi or CrP produced by Dob. We conclude that 1) ENDO perfusion abnormalities during tachycardia in LVH do produce ENDO subendocardial ischemia; 2) when the degree of augmentation of mechanical performance is considered, the metabolic changes induced by Dob were similar in normal and LVH hearts; 3) Dob-induced alterations in Pi and CrP were not related to inadequate perfusion, since increasing coronary BF did not reverse these changes; and 4) alterations of Pi and CrP during Dob infusion were not more prominent in the ENDO, indicating that the decreased ENDO/EPI flow did not cause ENDO ischemia but may reflect relatively lower O2 demands in this region during inotropic stimulation.

Adenosine Triphosphate↗
PubMed1993

Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. A comparison of signal characteristics with a biophysical model.

It recently has been demonstrated that magnetic resonance imaging can be used to map changes in brain hemodynamics produced by human mental operations. One method under development relies on blood oxygenation level-dependent (BOLD) contrast: a change in the signal strength of brain water protons produced by the paramagnetic effects of venous blood deoxyhemoglobin. Here we discuss the basic quantitative features of the observed BOLD-based signal changes, including the signal amplitude and its magnetic field dependence and dynamic effects such as a pronounced oscillatory pattern that is induced in the signal from primary visual cortex during photic stimulation experiments. The observed features are compared with the results of Monte Carlo simulations of water proton intravoxel phase dispersion produced by local field gradients generated by paramagnetic deoxyhemoglobin in nearby venous blood vessels. The simulations suggest that the effect of water molecule diffusion is strong for the case of blood capillaries, but, for larger venous blood vessels, water diffusion is not an important determinant of deoxyhemoglobin-induced signal dephasing. We provide an expression for the apparent in-plane relaxation rate constant (R2*) in terms of the main magnetic field strength, the degree of the oxygenation of the venous blood, the venous blood volume fraction in the tissue, and the size of the blood vessel.

Biophysical Phenomena↗
PubMed1993

Functional magnetic resonance imaging of Broca's area during internal speech.

Conventional gradient-echo magnetic resonance imaging (MRI) at 4 Tesla was used successfully to study the activity of Broca's area during internal speech word generation in healthy right-handed volunteers. Activity was demonstrated in the internal gray matter surrounding the ascending ramus of the lateral sulcus, deep to the cortical surface representation of Broca's area, in all the subjects. These studies demonstrate the capability of functional MRI to non-invasively map language related cognitive functions. Such functional mapping has value for both the study of basic neuroscience and neurosurgical planning.

Adult↗
PubMed1993

Functional imaging of human motor cortex at high magnetic field.

1. We used conventional gradient echo magnetic resonance imaging (MRI) at high field strength (4 Tesla) to functionally image the right motor cortex in six normal human subjects during the performance of a sequence of self-paced thumb to digit oppositions with the left hand (contralateral task), the right hand (ipsilateral task), and both hands (bilateral task). 2. A localized increase in activity in the lateral motor cortex was observed in all subjects during the task. The area of activation was similar in the contralateral and bilateral tasks but 20 times smaller in the ipsilateral task. The intensity of activation was 2.3 times greater in the contralateral than the ipsilateral task.

Adult↗
PubMed1993

Bioenergetic abnormalities associated with severe left ventricular hypertrophy.

Transmurally localized 31P-nuclear magnetic resonance spectroscopy (NMR) was used to study the effect of severe pressure overload left ventricular hypertrophy (LVH) on myocardial high energy phosphate content. Studies were performed on 8 normal dogs and 12 dogs with severe left ventricular hypertrophy produced by banding the ascending aorta at 8 wk of age. Spatially localized 31P-NMR spectroscopy provided measurements of the transmural distribution of myocardial ATP, phosphocreatine (CP), and inorganic phosphate (Pi); spectra were calibrated from measurements of ATP content in myocardial biopsies using HPLC. Blood flow was measured with microspheres. In hypertrophied hearts during basal conditions, ATP was decreased by 42%, CP by 58%, and the CP/ATP ratio by 32% in comparison with normal. Increasing myocardial blood flow with adenosine did not correct these abnormalities, indicating that they were not the result of persistent hypoperfusion. Atrial pacing at 200 and 240 beats per min caused no change in high energy phosphate content in normal hearts but resulted in further CP depletion with Pi accumulation in the inner left ventricular layers of the hypertrophied hearts. These changes were correlated with redistribution of blood flow away from the subendocardium in LVH hearts. These findings demonstrate that high energy phosphate levels and the CP/ATP ratio are significantly decreased in severe LVH. These abnormalities are proportional to the degree of hypertrophy but are not the result of persistent abnormalities of myocardial perfusion. In contrast, depletion of CP and accumulation of Pi during tachycardia in LVH are closely related to the pacing-induced perfusion abnormalities and likely reflect subendocardial ischemia.

Adenosine↗
PubMed1992

Dynamic mapping of the human visual cortex by high-speed magnetic resonance imaging.

We report the use of high-speed magnetic resonance imaging to follow the changes in image intensity in the human visual cortex during stimulation by a flashing checkerboard stimulus. Measurements were made in a 2.1-T, 1-m-diameter magnet, part of a Bruker Biospec spectrometer that we had programmed to do echo-planar imaging. A 15-cm-diameter surface coil was used to transmit and receive signals. Images were acquired during periods of stimulation from 2 s to 180 s. Images were acquired in 65.5 ms in a 10-mm slice with in-plane voxel size of 6 x 3 mm. Repetition time (TR) was generally 2 s, although for the long flashing periods, TR = 8 s was used. Voxels were located onto an inversion recovery image taken with 2 x 2 mm in-plane resolution. Image intensity increased after onset of the stimulus. The mean change in signal relative to the prestimulation level (delta S/S) was 9.7% (SD = 2.8%, n = 20) with an echo time of 70 ms. Irrespective of the period of stimulation, the increase in magnetic resonance signal intensity was delayed relative to the stimulus. The mean delay measured from the start of stimulation for each protocol was as follows: 2-s stimulation, delay = 3.5 s (SD = 0.5 s, n = 10) (the delay exceeds stimulus duration); 20- to 24-s stimulation, delay = 5 s (SD = 2 s, n = 20).

Brain Mapping↗